Selection and reversal of Plasmodium berghei resistance in the mouse model following repeated high doses of artemether Export

@article{citeulike:2586411, abstract = {Artemether, a derivative of artemisinin, is effectively used for the treatment of malaria without any clinically relevant resistance to date. Artemether has also been developed as an antischistosomal agent, exhibiting highest activity against immature parasites. Here, we employ a rodent model and investigate whether the proposed artemether treatment schedule to prevent schistosome-attributable morbidity might select for Plasmodium berghei resistance. Mice infected with an ANKA strain of P. berghei were treated with artemether at either 47\&\#160;mg/kg or 300\&\#160;mg/kg. Once every 7\&\#8211;10\&\#160;days, parasitized erythrocytes were passed to the next group of mice, receiving the same doses of artemether, for 50\&\#160;passages. Resistance development was slow but increased considerably over the final ten passages. At the higher dose of artemether, the indices of resistance were\&\#160;4.8 and\&\#160;8.8 after 40\&\#160;and 50\&\#160;passages, respectively. Importantly, resistance was unstable, since sensitivity reverted to near-normal after five passages without drug pressure. A moderate index of P. berghei resistance and no apparent reversibility was found in comparative experiments employing pyronaridine. In conclusion, the pace of resistance development in P. berghei to repeated high doses of artemether is slow and reversible.}, author = {Xiao, Shu-Hua and Yao, Jun-Min and Utzinger, J\"{u}rg and Cai, Yue and Chollet, Jacques and Tanner, Marcel}, citeulike-article-id = {2586411}, citeulike-linkout-0 = {http://dx.doi.org/10.1007/s00436-003-1029-9}, day = {1}, doi = {10.1007/s00436-003-1029-9}, journal = {Parasitology Research}, keywords = {delivery, drug, malaria}, month = {February}, number = {3}, pages = {215--219}, posted-at = {2008-03-25 16:07:11}, priority = {2}, title = {Selection and reversal of Plasmodium berghei resistance in the mouse model following repeated high doses of artemether}, url = {http://dx.doi.org/10.1007/s00436-003-1029-9}, volume = {92}, year = {2004} }

TY - JOUR ID - citeulike:2586411 L3 - citeulike-article-id:2586411 N2 - Artemether, a derivative of artemisinin, is effectively used for the treatment of malaria without any clinically relevant resistance to date. Artemether has also been developed as an antischistosomal agent, exhibiting highest activity against immature parasites. Here, we employ a rodent model and investigate whether the proposed artemether treatment schedule to prevent schistosome-attributable morbidity might select for Plasmodium berghei resistance. Mice infected with an ANKA strain of P. berghei were treated with artemether at either 47 mg/kg or 300 mg/kg. Once every 7–10 days, parasitized erythrocytes were passed to the next group of mice, receiving the same doses of artemether, for 50 passages. Resistance development was slow but increased considerably over the final ten passages. At the higher dose of artemether, the indices of resistance were 4.8 and 8.8 after 40 and 50 passages, respectively. Importantly, resistance was unstable, since sensitivity reverted to near-normal after five passages without drug pressure. A moderate index of P. berghei resistance and no apparent reversibility was found in comparative experiments employing pyronaridine. In conclusion, the pace of resistance development in P. berghei to repeated high doses of artemether is slow and reversible. IS - 3 JF - Parasitology Research EP - 219 TI - Selection and reversal of Plasmodium berghei resistance in the mouse model following repeated high doses of artemether VL - 92 SP - 215 KW - delivery KW - drug KW - malaria AU - Xiao, Shu-Hua AU - Yao, Jun-Min AU - Utzinger, Jürg AU - Cai, Yue AU - Chollet, Jacques AU - Tanner, Marcel PY - 2004/02/01/ UR - http://dx.doi.org/10.1007/s00436-003-1029-9 ER -